Global lung function initiative reference values for cardiopulmonary exercise testing

<bold>Background:</bold> Cardiopulmonary exercise testing (CPET) is used to assess individuals' physiological responses to exercise and to identify potential causes of exercise limitation. <bold>Aims and objectives:</bold> This study aimed to derive Global Lung Function Initiative (GLI) reference equations for peak oxygen uptake (V'O_2peak) and peak work rate (W_peak) in healthy individuals. <bold>Methods:</bold> CPET data were retrospectively collected from sites and underwent checks for consistency and quality. Generalised additive models of location, shape and scale (GAMLSS) were used to develop reference ranges, including age, sex, height, and weight as explanatory variables. The influence of geographic region, equipment, testing protocols and averaging methods for peak exercise data on the derived reference ranges was also examined. <bold>Results:</bold> Data from 6047 healthy individuals between 6 and 83 years across 17 sites in Europe, North and South America, and Asia were analysed. The final models explained 68.9% and 67.5% of the variability in V'O_2peak and W_peak, respectively. Variations persisted by site despite adjusting for key demographic factors. Geographic region, metabolic cart type, and averaging methods of peak exercise values improved model fit but were impractical as predictors for developing reference ranges. <bold>Conclusion:</bold> Significant heterogeneity in CPET testing methodology and outcomes between sites precluded the development of generalised reference ranges for V'O_2peak and W_peak. Further prospective studies with standardised CPET protocols and analytical methods are needed to reduce variability and establish robust, clinically meaningful interpretation strategies.